Matrine Mediated Immune Protection in MS by Regulating Gut Microbiota and Production of SCFAs.

There is clearly an unmet need for more effective and safer treatments for multiple sclerosis (MS). Our previous studies showed a significant therapeutic effect of matrine, a monomer of traditional herbal medicine, on experimental autoimmune encephalomyelitis (EAE) mice. To explore the mechanism of matrine action, we used 16S rRNA sequencing technology to determine the gut microbes in matrine-treated EAE mice and controls. The concentrations of short-chain fatty acids (SCFAs) were then tested by metabonomics. Finally, we established pseudo-sterile mice and transplanted into them fecal microbiota, which had been obtained from the high-dose matrine-treated EAE mice to test the effects of matrine. The results showed that matrine could restore the diversity of gut microbiota and promote the production of SCFAs in EAE mice. Transplantation of fecal microbiota from matrine-treated mice significantly alleviated EAE severity, reduced CNS inflammatory infiltration and demyelination, and decreased the level of IL-17 but increased IL-10 in sera of mice. In conclusion, matrine treatment can regulate gut microbiota and metabolites and halt the progression of MS.

Comparing Safety Profiles: Low-Temperature Plasma Excision vs. Traditional Adenoidectomy for Adenoid Hypertrophy.

Objective: This study compares the efficacy of low-temperature plasma excision and adenoidectomy performed under a nasal endoscope (NE) to treat adenoid hypertrophy (AH). The goal is to offer valuable insights and guidance for future treatments. Methods: We selected a cohort of 83 children diagnosed with AH admitted to our hospital between August 2019 and August 2022. The observation group included 45 children treated with low-temperature plasma excision under NE, while the control group consisted of 38 children treated with adenoidectomy under NE. We compared various parameters, including operative time, intraoperative bleeding, the time for white film disappearance, and the duration of hospitalization between the two groups. Additionally, we assessed levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), nasal pharyngeal volume (NPV), total inspiratory resistance (TIR), and total expiratory resistance (TER). Pain and sleep were evaluated using the Visual Analogue Scale (VAS) and the Pittsburgh Sleep Quality Index (PSQI). Finally, we recorded perioperative complications in both groups. Results: No significant difference was observed in the time of albuginea regression between the two groups (P > .05). However, the observation group demonstrated shorter operative time, quicker dietary recovery, and reduced hospital stay compared to the control group (P < .05). After treatment, the two groups had no significant differences in NPV, TIR, and TER (P > .05). Nevertheless, the observation group exhibited higher levels of SOD and GSH-Px, while MDA, CRP, TNF-α, IL-6, VAS, and PSQI scores were lower (P < .05). Furthermore, the incidence of complications in the observation group was significantly lower than in the control group (P < .05). Conclusions: Low-temperature plasma excision performed under NE for AH demonstrates superior outcomes and improved surgical safety and is strongly recommended for the treatment of adenoid hypertrophy.

Effective Treatment of Knee Osteoarthritis Using a Nano-Enabled Drug Acupuncture Technology in Mice.

A nano-enabled drug delivery acupuncture technology (nd-Acu) is developed that is based on traditional acupuncture needles where the stainless-steel surface is designed to deliver various payload molecules. To create the nd-Acu platform, an electrochemistry procedure is used to attach methyl salicylate-modified cyclodextrin in which the sugar rings allow the encapsulation of structurally defined single or multiple payload molecules via an inclusion complexation process. Drug loading and release profile are first studied using fluorescent dyes abiotically and at intact animal level. nd-Acu allows more efficient dye loading and time-dependent release compared to pristine needles without cyclodextrin modification. Subsequently, a proof-of-principle efficacy study is conducted using the platform to load a local anesthetic, lidocaine, for the treatment of knee osteoarthritis (KOA) in mice. It is demonstrated that lidocaine-laden nd-Acu can effectively alleviate pain, reduce inflammation, and slow down KOA development biochemically and histologically. Hypothesis-driven and proteomic approaches are utilized to investigate the working mechanisms of lidocaine nd-Acu, indicating that the therapeutic outcome is attributed to the in vivo modulation of the HMGB1/TLR4 signaling pathway. The study also obtained preliminary evidence suggesting the involvement of mitochondria as well as small GTPase such as cdc42 during the treatment by lidocaine nd-Acu.

Integrated metabolic and transcriptional analysis reveals the role of carotenoid cleavage dioxygenase 4 (IbCCD4) in carotenoid accumulation in sweetpotato tuberous roots.

BACKGROUND: Plant carotenoids are essential for human health, having wide uses in dietary supplements, food colorants, animal feed additives, and cosmetics. With the increasing demand for natural carotenoids, plant carotenoids have gained great interest in both academic and industry research worldwide. Orange-fleshed sweetpotato (Ipomoea batatas) enriched with carotenoids is an ideal feedstock for producing natural carotenoids. However, limited information is available regarding the molecular mechanism responsible for carotenoid metabolism in sweetpotato tuberous roots. RESULTS: In this study, metabolic profiling of carotenoids and gene expression analysis were conducted at six tuberous root developmental stages of three sweetpotato varieties with different flesh colors. The correlations between the expression of carotenoid metabolic genes and carotenoid levels suggested that the carotenoid cleavage dioxygenase 4 (IbCCD4) and 9-cis-epoxycarotenoid cleavage dioxygenases 3 (IbNCED3) play important roles in the regulation of carotenoid contents in sweetpotato. Transgenic experiments confirmed that the total carotenoid content decreased in the tuberous roots of IbCCD4-overexpressing sweetpotato. In addition, IbCCD4 may be regulated by two stress-related transcription factors, IbWRKY20 and IbCBF2, implying that the carotenoid accumulation in sweeetpotato is possibly fine-tuned in responses to stress signals. CONCLUSIONS: A set of key genes were revealed to be responsible for carotenoid accumulation in sweetpotato, with IbCCD4 acts as a crucial player. Our findings provided new insights into carotenoid metabolism in sweetpotato tuberous roots and insinuated IbCCD4 to be a target gene in the development of new sweetpotato varieties with high carotenoid production.

Early complementary acupuncture improves the clinical prognosis of traumatic brain edema: A randomized controlled trial.

BACKGROUND: Traumatic brain edema occurs commonly brain injury, and most manifests as pericontusional edema of brain contusions. On the basis of evidence-based medicine, apart from recommending craniotomy and mannitol, there are few particularly effective measures to prevent and treat traumatic brain edema. It is uncertain whether an early complementary acupuncture treatment would improve long-term outcomes of patients with traumatic brain edema. The aim of this study is to assess the efficacy and the safety of early complementary acupuncture for patients with traumatic brain edema. METHODS: This study is an actively accruing, single-center, single-blinded, 2-arm, randomized controlled trial. Patients with traumatic brain injury, a Glasgow Coma Scale score of 6∼12, and brain edema on computed tomography scan will be divided into 2 groups on the basis of stratified block randomization. All patients will receive conventional treatment, and the study group will undergo additional acupuncture therapy (start within 72 hours after the injury) once a day for 28 days. The primary outcome is the dichotomized Glasgow Outcome Score at 6 months and 12 months after injury, and the secondary outcomes are the Glasgow Coma Scale, the volume of traumatic brain edema, the serum levels of C-reactive protein and interleukin-6, and the Modified Barthel Index. DISCUSSION: This study will provide data regarding the efficacy of early complementary acupuncture for traumatic brain edema. If the study yields positive results, its findings may offer insights into a valuable complementary option of acupuncture for traumatic brain edema that could provide pilot evidence for large, randomized, controlled trials.Trial registration: This trial has been published in the Chinese Clinical Trial Register, http://www.chictr.org.cn/edit.aspx?pid=141208&htm=4 (Identifier: ChiCTR2100053794, registered on December 3, 2021).

Supplementing conjugated linoleic acid in breeder hens diet increased conjugated linoleic acid incorporation in liver and alters hepatic lipid metabolism in chick offspring.

This experiment was designed to investigate the effect of supplementing conjugated linoleic acid (CLA) in breeder hens diet on development and hepatic lipid metabolism of chick offspring. Hy-Line Brown breeder hens were allocated into two groups, supplemented with 0 (control (CT)) or 0·5 % CLA for 8 weeks. Offspring chicks were grouped according to the mother generation and fed for 7 d. CLA treatment had no significant influence on development, egg quality and fertility of breeder hens but darkened the egg yolks in shade and increased yolk sac mass compared with the CT group. Addition of CLA resulted in increased body mass and liver mass and decreased deposition of subcutaneous adipose tissue in chick offspring. The serum TAG and total cholesterol levels of chick offspring were decreased in CLA group. CLA treatment increased the incorporation of both CLA isomers (c9t11 and t10c12) in the liver of chick offspring, accompanied by the decreased hepatic TAG levels, related to the significant reduction of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) enzyme activities and the increased carnitine palmitoyltransferase-1 (CPT1) enzyme activity. Meanwhile, CLA treatment reduced the mRNA expression of genes related to fatty acid biosynthesis (FAS, ACC and sterol regulatory element-binding protein-1c) and induced the expression of genes related to ß-oxidative (CPT1, AMP-activated protein kinase and PPARα) in chick offspring liver. In summary, the addition of CLA in breeder hens diet significantly increased the incorporation of CLA in the liver of chick offspring, which further regulate hepatic lipid metabolism.

A Novel Bionic Catalyst-Mediated Drug Delivery System for Enhanced Sonodynamic Therapy.

Ultrasound (US)-triggered sonodynamic therapy (SDT) proves itself to be a formidable tool in the fight against cancer, due to its large spectrum of uses as a non-invasive therapeutic measure, while also demonstrating itself to be a certain improvement upon traditional SDT therapeutics. However, tumor hypoxia remains to be a major challenge for oxygen-dependent SDT. This study describes the development of an innovative, multi-use, catalyst-based and improved SDT targeting cancer, through the employment of a sonosensitizing curcumin (Cur) load embedded within a MnO2 core, together with an extraneous tumor cell membrane component. The latter allows for efficient tumor recognition properties. Hollowed-out MnO2 allows for efficient drug delivery, together with catalyzing oxygen generation from hydrogen peroxide present in tumor tissue, leading to enhanced SDT efficacy through the induction of a reduced hypoxic state within the tumor. In addition, Cur acts as a cytotoxic agent in its own right. The results deriving from in vivo studies revealed that such a biomimetic approach for drug-delivery actually led to a reduced hypoxic state within tumor tissue and a raised tumor-inhibitory effect within mouse models. Such a therapeutic measure attained a synergic SDT-based tumor sensitization treatment option, together with the potential use of such catalysis-based therapeutic formulations in other medical conditions having hypoxic states.

Illumination of Molecular Pathways in Multiple Sclerosis Lesions and the Immune Mechanism of Matrine Treatment in EAE, a Mouse Model of MS.

The etiology of multiple sclerosis (MS) is not clear, and the treatment of MS presents a great challenge. This study aimed to investigate the pathogenesis and potential therapeutic targets of MS and to define target genes of matrine, a quinolizidine alkaloid component derived from the root of Sophorae flavescens that effectively suppressed experimental autoimmune encephalomyelitis (EAE), an animal model of MS. To this end, the GSE108000 gene data set in the Gene Expression Omnibus Database, which included 7 chronic active MS lesions and 10 control samples of white matter, was analyzed for differentially expressed genes (DEGs). X cell was used to analyze the microenvironmental differences in brain tissue samples of MS patients, including 64 types of immune cells and stromal cells. The biological functions and enriched signaling pathways of DEGs were analyzed by multiple approaches, including GO, KEGG, GSEA, and GSVA. The results by X cell showed significantly increased numbers of immune cell populations in the MS lesions, with decreased erythrocytes, megakaryocytes, adipocytes, keratinocytes, endothelial cells, Th1 cells and Tregs. In GSE108000, there were 637 DEGs, including 428 up-regulated and 209 down-regulated genes. Potential target genes of matrine were then predicted by the network pharmacology method of Traditional Chinese medicine, and 12 key genes were obtained by cross analysis of the target genes of matrine and DEGs in MS lesions. Finally, we confirmed by RT-PCR the predicted expression of these genes in brain tissues of matrine-treated EAE mice. Among these genes, 2 were significantly downregulated and 6 upregulated by matrine treatment, and the significance of this gene regulation was further investigated. In conclusion, our study defined several possible matrine target genes, which can be further elucidated as mechanism(s) of matrine action, and novel targets in the treatment of MS.

Simultaneous identification of Fritillariae cirrhosae bulbus and its common adulterants in one reaction by multiplex ligation-dependent probe amplification and high-resolution melting curve assay.

Fritillariae cirrhosae bulbus, a well-known and precious medicinal and edible herb in China, causes remarkable effects on swelling and relieving cough, with fewer side effects than other congeneric medicine. It has been subject to various cheaper congeneric adulteration because of its high price and limited production. In this paper, a rapid, high throughput, sensitive and efficient technique was described for simultaneous identification of F. cirrhosae bulbus and its common adulterants by employing multiplex ligation-dependent probe amplification coupled with high-resolution melting (MLPA-HRM) curve assay in their internal transcribed spacer 1 (ITS1) regions. This assay was highly sensitive with a detection limit of 0.19 ng genomic DNA, and highly specific with no cross-reaction with common adulterants. Mixed sample analysis showed as low as 10% adulteration can be detected from F. cirrhosae bulbus in one MLPA-HRM reaction. Overall, the method described in this paper is well suited for detecting adulteration in F. cirrhosae bulbus.

A novel circular RNA, circ-ATAD1, contributes to gastric cancer cell progression by targeting miR-140-3p/YY1/PCIF1 signaling axis.

Circular RNAs (circRNAs) has been shown to be involved in the progression of various malignancies. Nevertheless, the mechanism of dysregulated circRNAs in gastric cancer (GC) remains to be understood. CircRNA microarray was utilized for identifying circRNA expression profiles in GC tissues. Circ-ATAD1 expression was measured by qRT-PCR. The clinical significance of circ-ATAD1 was analyzed by Fisher's exact test, Kaplan-Meier plots, and Cox regression model. The function of circ-ATAD1 was explored by using CCK-8, clone formation, flow cytometric and transwell experiments. RNA sequencing, bioinformatics, RNA pulldown, chromatin immunoprecipitation followed by sequencing, and dual-luciferase reporter assays were applied to determine the regulatory networks of circ-ATAD1 in GC cells. Circ-ATAD1 expression was increased in cancerous tissues. The prognostic value of circ-ATAD1 was identified in GC patients. For GC cells, circ-ATAD1 increased cell progression by sponging miR-140-3p to upregulate YY1. Additionally, YY1 directly bound to the promoter of PCIF1, thereby activating its transcription. Collectively, circ-ATAD1 plays an important role in GC tumorigenesis and progression and might be an important biomarker/therapeutic target for GC.

[Randomized clinical trials of early acupuncture treatment of limb paralysis in traumatic brain injury patients and its mechanism].

OBJECTIVE: To observe the clinical effect of early acupuncture treatment of limb paralysis in patients with traumatic brain injury (TBI) and changes of serum interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels, so as to explore its mechanism underlying improvement of TBI. METHODS: A total of 70 TBI inpatients were equally divided into a medication group and an acupuncture plus medication group according to a random number table. The medication contained intravenous drip of Mannitol Injection (125 mL, once every 8 h ) and Oxiracetam Injection (4 g, once a day). Starting 72 h after TBI, acupuncture therapy was applied to main points as Fenglong (ST40), Zusanli (ST36), Guanyuan (CV4), Baihui (GV20), Shuigou (GV26) and Fengchi (GB20), etc. The treatment was given once a day for total 28 days. Before and after the treatment, plasma IL-6, BDNF and NGF contents were detected using radioimmunoassay, the volume of the injured brain tissue was detected by using CT scan. The neurological deficit severity was evaluated by using Glasgow Coma Scale (GCS), and the degree of activity of daily living (ADL) ability was assessed by using simplified Fugl-Meyer assessment (FMA) scale, and modified Barthel index (BI), separately. RESULTS: After the treatment, the GCS score on day 28, FMA and ADL-BI scores on day 28 and 60 were significantly increased in both medication and acupuncture plus medication groups in comparison with their own pre-treatment (P<0.05). The focal volume values of the injured brain were significantly decreased on day 14 and 28 in both groups compared with their own pre-treatment (P<0.05). The therapeutic effect of acupuncture plus medication was obviously superior to that of simple medication in lowering focal injured volume on day 14 and 28, and in increasing FMA and ADL-BI scores on day 28 and 60 (P<0.05). Compared with pre-treatment, the levels of plasma IL-6 on day 3, 7 and 14 were significant decreased, and those of plasma BDNF and NGF on day 3, 7 and 14 considerably increased in both groups in comparison with their own pre-treatment (P<0.05). The therapeutic effect of acupuncture plus medication was evidently superior to that of simple medication in lowering IL-6 on day 3 and 7, and in increasing BDNF and NGF levels on day 3, 7 and 14 (P<0.05). CONCLUSION: Early acupuncture treatment can significantly improve the TBI patient's limb motor function and daily life activities, which may be related with its effects in reducing the inflammation and increasing BDNF and NGF levels.

Trimetazidine ameliorates myocardial ischemia-reperfusion injury.

Aim of this study was to investigate the effects of trimetazidine attenuating the myocardial ischemia-reperfusion injury to myocardium in rats and the underlying mechanisms. A model of myocardial ischemia reperfusion was established via ligating the left anterior descending coronary artery in 30 rats, and then they were randomly assigned to model group (n=10), low dose group (n=10) and high dose group (n=10). Moreover, additional 10 rats were collected and allocated to sham operation group, which was served as control group. Then, rats in the low dose group and high dose group were given trimetazidine with the dose of 10mg/kg and 30mg/kg respectively by intragastric administration, while rats in the control group and model group were given the equivalent volume saline. The dose was given once a day for consecutive 4 weeks in all rats. Echocardiography was applied to evaluate cardiac function, including left ventricular end-systolic dimension (LVESD), left ventricular end diastolic dimension (LVEDD) and left ventricular ejection fraction (LVEF). Next, myocardial tissue was collected, and Bax and Bcl-2 mRNA and the protein levels in the four groups were detected by RT-PCR and Western blot respectively. The level of malonaldehyde (MDA) and super oxide dismutase (SOD) activity in rat myocaridum in each group were detected by colorimetric methods, while the variables of apoptosis were measured by TUNEL methods. In comparison with the control group, LVEDD, LVEDS of rats increased significantly, LVEF decreased obviously, as well as Bax level, MDA level and the apoptotic variables in myocardial tissue increased (P<0.05), but Bcl-2 level and SOD activity decreased significantly in low dose, high dose and model group (P<0.05). Compared with model group, LVEDD, LVEDS of rats decreased obviously, LVEF increased significantly, as well as Bax level, MDA level and the apoptotic variables in myocardial tissue decreased (P<0.05), but Bcl-2 level and SOD activity increased significantly in low dose group, high dose group (P<0.05). The regulatory role of trimetazidine on above indicators of rats was in a dose-dependent manner. Trimetazidine can ameliorate rat myocardium following ischemia-reperfusion injury by effectively attenuating the injury from myocardial cell apoptosis; meanwhile, it can resist cell apoptosis through regulating Bax and bcl-2 expression, which exhibits guiding significance for the treatment of myocardial ischemia and reperfusion.

[Early acupuncture for traumatic intracerebral hematoma: a randomized controlled trial].

OBJECTIVE: To observe the effect of early acupuncture intervention on brain edema in patients with traumatic intracerebral hematoma and explore its mechanism on the basis of conventional western medicine. METHODS: With stratified block randomization, sixty-four patients with glasgow coma scale (GCS) of 6 to 12 were divided into an acupuncture combined with medicine group (a combination group) and a western medication group, 32 cases in each one. In the western medication group, dehydration to reduce intracranial pressure and nutritional nerves were given as the basic treatment. In the combination group, on the basis of the treatment as the western medication group, acupuncture was applied at Xuehai (SP 10), Taixi (KI 3), Fenglong (ST 40), Yinlingquan (SP 9), Zusanli (ST 36), etc. The treatment was given once every day, for 6 times as one course; there was an interval of 1 day between two courses; a total of 4 courses were required. GCS score and recovery time were recored before treatment and on the 7 th, 14 th and 28 th days. 90 days follow-up after treatment, the GOS was observed, and the mortality and effective survival rate were calculated. The Barthel index (BI) score was evaluated before treatment and on the 14th, 21st, 28th days and 90 days follow-up after treatment. Before treatment and 3rd, 7th, 14th, 21st, 28th days, cranial CT or MR scan was performed to calculate the brain edema index (BEI); Plasma interleukin-6 (6IL-6), neuropeptide Y (NPY) and nitric oxide (NO) were measured before treatment and on the 3rd, 7th and 14th days after treatment. RESULTS: (1) The GCS scores increased gradually in the two groups during treatment, and there was significant difference between the 28th days and before treatment (both P<0.05). There were no significant difference between the two groups about GCS score and average recovery time on the 28th days treatment (all P>0.05). (2) The mortality rate of the combination group was 6.3% (2/32) on 90 days follow-up, 9.4% (3/32) in the western medication group (P>0.05). The effective survival rate was 81.3% (26/32) in the combination group, which was higher than 59.4% (19/32) in the western medication group (P<0.05). (3) The BI score was significantly higher than that before treatment on the 28th days and 90 days follow-up in the two groups (all P<0.05), and the result in the combination group was superior to that in the western medication group (both P <0.05). (4) The BEI decreased on the 14th, 21st and 28th days in the two groups (all P<0.05), and on the 14th day, the BEI decreased more significantly in the combination group than that in the western medication group (P<0.05). (5) The levels of IL-6, NPY and NO decreased on the 7th and 14th days in the two groups (all P<0.05), and decreased more significantly in the combination group than that in the western medication group on the 7th day (P<0.05). CONCLUSION: On the basis of conventional western medicine, early acupuncture can reduce cerebral edema and improve the prognosis of patients, and acupuncture combined with medicine are superior to western medicine alone. Acupuncture mechanism may be related to reducing the expression of inflammatory response.

Potential application of pre-treated municipal solid waste incineration fly ash as cement supplement.

Pre-treatment process carried out on raw municipal solid waste incineration (MSWI) fly ash (FA) sample that did not comply initially with the USEPA method 1311 toxicity characteristic leaching procedure (TCLP) regulatory limits of 2011 reduced its chloride and heavy metal content appreciably, thereby making it compliant with the aforementioned regulatory requirement. More than 98% of each heavy metal was successfully removed. The process was excellent in removing cadmium (Cd) (99.99%) and very good at removing the rest. About 99.96% of Cu was eliminated, 99.96% of cobalt (Co), 99.95% of Zn, 98.61% of Cr, and 98.12% of nickel (Ni). Also, the leachate resulting from these pre-treatment steps met the China (GB 16889-2008) and USEPA method 1311 regulatory standards for safe discharge. The density and compressive strength of all the samples prepared increased as the FA content decreased. The compressive strength of all the samples passed the 1989 USEPA-recommended value of 0.34 MPa (50 psi), thereby making them suitable for industrial application. The sample that attained the highest compressive strength (2.08 MPa) after 28 days of curing incorporated 55% fly ash (FACS55), while the one with the least compressive strength (0.65 MPa) after the same period was made from only fly ash (FACS100). Moreover, the concentration of heavy metals in all the samples generally decreased with the FA content. Chromium was not detected in all the samples, thereby making this an excellent method for its immobilization. From the leachability test results, all the samples prepared met the USEPA method 1311 TCLP regulatory limits.

The Complete Chloroplast Genome Sequences of the Medicinal Plant Forsythia suspensa (Oleaceae).

Forsythia suspensa is an important medicinal plant and traditionally applied for the treatment of inflammation, pyrexia, gonorrhea, diabetes, and so on. However, there is limited sequence and genomic information available for F. suspensa. Here, we produced the complete chloroplast genomes of F. suspensa using Illumina sequencing technology. F. suspensa is the first sequenced member within the genus Forsythia (Oleaceae). The gene order and organization of the chloroplast genome of F. suspensa are similar to other Oleaceae chloroplast genomes. The F. suspensa chloroplast genome is 156,404 bp in length, exhibits a conserved quadripartite structure with a large single-copy (LSC; 87,159 bp) region, and a small single-copy (SSC; 17,811 bp) region interspersed between inverted repeat (IRa/b; 25,717 bp) regions. A total of 114 unique genes were annotated, including 80 protein-coding genes, 30 tRNA, and four rRNA. The low GC content (37.8%) and codon usage bias for A- or T-ending codons may largely affect gene codon usage. Sequence analysis identified a total of 26 forward repeats, 23 palindrome repeats with lengths >30 bp (identity > 90%), and 54 simple sequence repeats (SSRs) with an average rate of 0.35 SSRs/kb. We predicted 52 RNA editing sites in the chloroplast of F. suspensa, all for C-to-U transitions. IR expansion or contraction and the divergent regions were analyzed among several species including the reported F. suspensa in this study. Phylogenetic analysis based on whole-plastome revealed that F. suspensa, as a member of the Oleaceae family, diverged relatively early from Lamiales. This study will contribute to strengthening medicinal resource conservation, molecular phylogenetic, and genetic engineering research investigations of this species.

Design, synthesis and biological evaluation of bisabolangelone oxime derivatives as potassium-competitive acid blockers (P-CABs).

With the aim of searching novel P-CABs, seven bisabolangelone oxime derivatives were designed, synthesized, characterized and evaluated the H(+),K(+)-ATPase inhibitory activities guided by computer aided drug design methods. The binding free energy calculations were in good agreement with the experiment results with the correlation coefficient R of -0.9104 between ΔGbind and pIC50 of ligands. Compound 5 exhibited the best inhibitory activity (pIC50=6.36) and most favorable binding free energy (ΔGbind=-47.67 kcal/mol) than other derivatives. The binding sites of these compounds were found to be the hydrophobic substituted groups with the Cys813 residue by the decomposed binding free energy analysis.

Surgical resection should be taken into consideration for the treatment of small gastric gastrointestinal stromal tumors.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) recommends conservative follow-up for gastric gastrointestinal stromal tumors (GISTs) less than 2 cm. The aim of the present study was to investigate the clinical and pathological features of small gastric GISTs, re-evaluate the risk potential, and discuss the treatment strategy of small gastric GISTs. METHODS: In this retrospective study, 63 cases of small gastric GISTs (less than 2 cm) were resected surgically from May 2010 to March 2013 in our department. Clinicopathological factors were collected and the malignant potential of small gastric GISTs was analyzed. RESULTS: The mitotic index of 14 out of 63 cases (22.22%) exceeded 5. The malignant potential of small gastric GISTs was related to tumor location (P = 0.0218). The mitotic index of 4 out of 8 GISTs (50%) located in gastric cardia exceeded 5, 8 out 28 GISTs (28.57%) located in the gastric fundus exceeded 5, and only 2 out of 27 GISTs (7.41%) located in the gastric body exceeded 5. We also discovered a good consistency between mitotic index and Ki-67 expression of small gastric GISTs. CONCLUSIONS: Gastric GISTs less than 2 cm also have malignant potential. Thus, we recommended surgical resection of all small gastric GISTs once diagnosed.

Enhanced potency of individual and bivalent DNA replicon vaccines or conventional DNA vaccines by formulation with aluminum phosphate.

DNA vaccines against botulinum neurotoxin (BoNTs) induce protective humoral immune responses in mouse model, but when compared with conventional vaccines such as toxoid and protein vaccines, DNA vaccines often induce lower antibody level and protective efficacy and are still necessary to increase their potency. In this study we evaluated the potency of aluminum phosphate as an adjuvant of DNA vaccines to enhance antibody responses and protective efficacy against botulinum neurotoxin serotypes A and B in Balb/c mice. The administration of these individual and bivalent plasmid DNA replicon vaccines against botulinum neurotoxin serotypes A and B in the presence of aluminum phosphate improved both antibody responses and protective efficacy. Furthermore, formulation of conventional plasmid DNA vaccines encoding the same Hc domains of botulinum neurotoxin serotypes A and B with aluminum phosphate adjuvant increased both antibody responses and protective efficacy. These results indicate aluminum phosphate is an effective adjuvant for these two types of DNA vaccines (i.e., plasmid DNA replicon vaccines and conventional plasmid DNA vaccines), and the vaccine formulation described here may be an excellent candidate for further vaccine development against botulinum neurotoxins.

[Real-time process control of denitrifying phosphorus and nitrogen removal systems with NO3(-) and NO2(-) as electron acceptors].

The simultaneous phosphorus and nitrogen removal using denitrifying phosphate-accumulating organisms with NO3(-) and NO2(-) as electron acceptors was investigated in an anaerobic/anoxic process. The results showed that the concentrations of COD, PO4(3-) and electron acceptors (NO3(-) and NO2(-)) have a correlation with the variation of pH and ORP during anaerobic/anoxic process. In anaerobic phase, the occurrence of pH flat indicates the end of phosphorus release. In anoxic process, an inflexion was observed in ORP profile when the phosphorus uptake was finished. In addition, the phosphorus uptake rate was investigated in the process with different electron acceptors (NO3(-) and NO2(-)). The average anoxic phosphate uptake rate was 32.68 mg/(L x h) in the early 30 min during anoxic phase when NO3(-) was as electron acceptor, and every 1 mg PO4(3-)-P uptake would consume 1.14 mg NO3(-)-N. In the process with NO2(-) as electron acceptor, the average anoxic phosphate uptake rate was 17.66 mg/(Lx h) in the early 30 min, and every 1 mg PO4(3-)-P uptake would consume 1.57 mg NO2(-)-N. In conclusion, ORP and pH can be used as control parameters for simultaneous phosphorus and nitrogen removal in an anaerobic/anoxic process, and the system with NO3(-) as electron acceptor is superior to the system with NO2(-) as electron acceptor.